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DNA repair is a most important cellular process that helps maintain the integrity of the genome and is currently considered by researchers as one of the factors determining the maximum lifespan. The central regulator of the DNA repair process is the enzyme poly(ADP-ribose)polymerase 1 (PARP1). PARP1 catalyzes the synthesis of poly(ADPribose) polymer (PAR) upon DNA damage using nicotinamide adenine dinucleotide (NAD+) as a substrate. This polymer covalently attaches to PARP1, which leads to its dissociation from the complex with damaged DNA and stimulation of the repair process. Despite intensive research on PARP1, its properties as an isolated protein have not been practically studied in mammals that demonstrate a long maximum lifespan, such as, for example, the naked mole rat (Heterocephalus glaber). High activity of DNA repair systems is observed in the cells of the naked mole rat, which ensures their high resistance to oxidative stress, as well as to genotoxic effects. The revealed features may be due to the high activity of PARP1 in the cells of the naked mole rat; however, this issue remains poorly understood and, thus, requires more detailed research, including one with the use of isolated protein PARP1 of the naked mole rat, the isolation and characterization of which have not been carried out before. In the present work, the amino acid sequence of PARP1 of the naked mole rat is compared with the amino acid sequences of orthologous proteins of other mammals. In contrast to human PARP1, 13 evolutionarily conservative amino acid substitutions in various functional domains of the protein have been identified in the amino acid sequence of naked mole rat PARP1. Using the cDNA of the naked mole rat’s Parp1 gene, a vector was created for the expression of the target protein in Escherichia coli cell culture. For the first time, a detailed description of the procedure for the expression and purification of the recombinant protein PARP1 of the long-lived naked mole rat is presented. In addition, poly(ADP-ribose)polymerase activity of the obtained protein was evaluated. The results presented in this paper are the basis for further detailed characterization of the properties of purified recombinant naked mole rat PARP1.

Chronic pancreatitis (CP) is a progressive benign fibroinflammatory condition involving repeated episodes of pancreatic inflammation, which lead to fibrotic tissue replacement and subsequent pancreatic insufficiency. A lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC) in patients with chronic pancreatitis is reported to be 1.5%-4%. However, diagnosis of PDAC in patients with CP can be challenging, in part due to overlapping imaging features. In rare instances, pancreatic parenchymal calcifications that are typically associated with chronic pancreatitis may diminish in the case of a developing PDAC. In this article, we present a patient with chronic pancreatitis in whom calcifications decreased at the time of pancreatic ductal adenocarcinoma diagnosis, as compared to prior CT imaging. The unique imaging features of “diminishing calcifications” associated with a hypoattenuating lesion can potentially be a useful sign of pancreatic ductal adenocarcinoma and may aid in early diagnosis and prompt treatment intervention.

Abstract Surveys often estimate vaccination intentions using dichotomous ("Yes"/"No") or trichotomous ("Yes," "Unsure," "No") response options presented in different orders. Do survey results depend on these variations? This controlled experiment randomized participants to dichotomous or trichotomous measures of vaccine intentions (with “Yes” and “No” options presented in different orders). Intentions were measured separately for COVID-19, its booster, and influenza vaccines. Among a sample of U.S. adults (N = 4,764), estimates of vaccine intention varied as much as 37.5 ± 17.4 percentage points as a function of the dichotomous or trichotomous response set. Among participants who had not received the COVID-19 vaccine, the “Unsure” option was more likely to reduce the share of “No” (versus “Yes”) responses, whereas among participants who had received the COVID-19 vaccine, the “Unsure” option was more likely to reduce the share of “Yes” (versus “No”) responses. The “Unsure” category may increase doubt and decrease reliance on past vaccination behavior when forming intentions. The order of “Yes” and “No” responses had no significant effect. Future research is needed to further evaluate why the effects of including the “Unsure” option vary in direction and magnitude.

COVID-19 vaccination rates remain lower among adolescents compared with adults. Youth participatory action research (YPAR) offers opportunities to inform youth vaccine communication at the local and population level. However, few studies have integrated systematic health communication research with YPAR. In the current study, a diverse team of paid high school interns, undergraduate student mentors and communication researchers in West Philadelphia YPAR programs developed a theory-informed communication survey to measure teen COVID-19 vaccine beliefs, information sources and behavior. The survey was distributed locally and informed youth-created vaccine campaign messages. In addition, YPAR-derived survey measures complimented a qualitative online elicitation survey with US young adults. Responses were coded using inductive content analysis, informing measures for a subsequent population-level study of young adults. This research followed protocols approved by an Institutional Review Board. Applying a YPAR framework elevated youth voices in the study development process. Communication theory and methods aided the development of survey studies to advance both local YPAR program objectives and population-level research. Future implications are discussed.

The nature of enhanced photoemission in disordered and amorphous solids is anintriguing open question. A point in case is light emission in silicon, whichoccurs when the material is porous or nanostructured, but the effect is absentin the bulk crystalline phase, a phenomenon that is still not fully understood.In this work, we study structural photoemission in a heterogeneous cross-linkedsilicon glass, a material that represents an intermediate state between theamorphous and crystalline phases, characterized by a narrow distribution ofstructure sizes. This model system shows a clear dependence of photoemission onsize and disorder across a broad range of energies. While phonon-assistedindirect optical transitions are insufficient to describe observable emissions,our experiments suggest these can be understood through electronic Ramanscattering instead. This phenomenon, not commonly observed in crystallinesemiconductors, is driven by structural disorder. We attribute photoemission inthis disordered system to the presence of an excess electron density of stateswithin the forbidden gap (Urbach bridge), where electrons occupy trappedstates. Transitions from gap states to the conduction band are facilitatedthrough electron-photon momentum matching, which resembles Compton scattering,but observed for visible light and driven by the enhanced momentum of a photonconfined within the nanostructured domains. We interpret the light emission instructured silicon glass as resulting from electronic Raman scattering. Thesefindings emphasize the role of photon momentum in the optical response ofsolids that display disorder at the nanoscale.

Seminoma is a malignant germ cell tumor that primarily develops in the testis but can occur in other extragonadal areas, most commonly the mediastinum and retroperitoneum. While generally offering a favorable prognosis, seminomas can sometimes clinically present with misleading characteristics resulting in delayed diagnosis. In this article, we report the case of a 31-year-old male diagnosed with grade IIIC intermediate risk testicular seminoma cTxN3M1bSx, who presented initially with a palpable cervical mass. We focus on the use of radiological modalities for an optimized diagnosis by coordinating our imaging with pathological findings and clinical presentation.

Leiomyoma of the bladder is an unusual cause of benign smooth muscle tumor, only reported about 250 times in the literature. Imaging studies including computed tomography (CT) and magnetic resonance imaging (MRI) scans are useful in defining the extent and location of the tumor, however, immunohistology samples must be obtained to rule out similar appearing cancerous masses. In this article, we report the case of a 50-year-old male diagnosed with leiomyoma of the bladder that initially presented as dysuria and raised suspicion of a bladder transitional cell carcinoma (TCC). We focus on the utilization of radiological imaging modalities for diagnosis, management, and preoperational planning with pathological findings for an optimized diagnosis.

Abstract Alloying in metal castings is one of the principal methods of strengthening an alloy for various structural and functional applications, but very rarely does it modify an alloy’s elastic modulus. We report a methodology of combining isostructural Laves phases to form a multi-component, high symmetry, isotropic phase that was discovered to enhance the elastic modulus of a cast aluminum alloy to 91.5 ± 7.4 GPa. Flux grown single crystals of the rhombicuboctahedron phase (RCO), so named for the observed morphology, were used to enhance understanding of the structure and mechanical properties of the phase. The pure RCO phase’s structure and site occupancies were co-refined using x-ray and neutron diffraction. Dynamic nanomechanical testing of the cast alloy shows the primary RCO phase has a high, relatively isotropic, elastic modulus. This RCO containing aluminum alloy is found to have a specific modulus that exceeds that of the leading Al, Mg, Steel, and Ti alloys.

Endometriosis is a chronic disease characterized by the presence and growth of endometrial glands and stroma outside of the uterine cavity. The pathogenesis is unclear, but a common theory attributes the condition to retrograde menstruation into the peritoneal cavity via the fallopian tubes. Hormonal influence causes these ectopic tissues to undergo cyclical bleeding, resulting in subsequent inflammation and scar tissue formation; however, it can affect postmenopausal women. In rare instances, endometriotic lesions can obstruct the ureter and result in hydroureteronephrosis and subsequent loss of renal function. This condition presents with nonspecific symptoms and is known as an often-silent disease, resulting in challenging and delayed preoperative diagnosis. In this article, we report the case of an asymptomatic 65-year old female who was diagnosed with deep pelvic endometriosis, which obstructed the right distal ureter. We focus on optimizing diagnosis and management through the application of radiological imaging modalities, specifically computed tomography (CT) and magnetic resonance imaging (MRI).

Abstract Hypophosphatemia (serum phosphate

Abstract In order to facilitate cardiovascular research to develop non-invasive optical heart pacing methods, we have generated a double-transgenic Drosophila melanogaster (fruit fly) model suitable for optogenetic pacing. We created a fly stock with both excitatory H134R-ChR2 and inhibitory eNpHR2.0 opsin transgenes. Opsins were expressed in the fly heart using the Hand-GAL4 driver. Here we describe Hand > H134R-ChR2; eNpHR2.0 model characterization including bi-directional heart control (activation and inhibition) upon illumination of light with distinct wavelengths. Optical control and real-time visualization of the heart function were achieved non-invasively using an integrated light stimulation and optical coherence microscopy (OCM) system. OCM produced high-speed and high-resolution imaging; simultaneously, the heart function was modulated by blue (470 nm) or red (617 nm) light pulses causing tachycardia, bradycardia and restorable cardiac arrest episodes in the same animal. The irradiance power levels and illumination schedules were optimized to achieve successful non-invasive bi-directional heart pacing in Drosophila larvae and pupae.

Abstract Maternal malnutrition has been associated with neurodevelopmental deficits and long-term implications on the offspring’s health and behavior. Here, we investigated the effects of maternal low-protein diet (LPD) or obesity-inducing maternal high-fat diet (HFD) on dyadic social interactions, group organization and autism-related behaviors in mice. We found that maternal HFD induced an autism-related behavioral phenotype in the male offspring, including a robust decrease in sociability, increased aggression, cognitive rigidity and repetitive behaviors. Maternal LPD led to a milder yet significant effect on autism-related symptoms, with no effects on olfactory-mediated social behavior. Under naturalistic conditions in a group setting, this manifested in altered behavioral repertoires, increased magnitude in dominance relations, and reduced interactions with novel social stimuli in the HFD male offspring, but not in the LPD offspring. Finally, we found HFD-induced transcriptomic changes in the olfactory bulbs of the male offspring. Together, our findings show that maternal malnutrition induces long-lasting effects on aggression and autism-related behaviors in male offspring, and potential impairments in brain regions processing chemosensory signals.

Abstract Background The hypothalamic–pituitary–adrenal (HPA) and -gonadal (HPG) axes are two major pathways that connect the neural and endocrine systems in vertebrates. Factors such as prenatal stress and maternal exposure to exogenous steroids have been shown to affect these pathways during fetal development. Another less studied factor is the transfer of hormones across fetuses in multifetal pregnancies. This form of transfer has been shown to influence the morphology, anatomy, physiology, and behavior of the offspring in litter-bearing mammals, an influence termed the intrauterine position (IUP) effect. In this study, we sought to delineate how the IUP effects HPA and HPG brain receptors, peptides, and enzymes (hereafter components) in utero and how these influences may differ between males and females. Methods We utilized the unconventional model of culled free-ranging nutria (Myocastor coypus), with its large natural variation. We collected brain tissues from nutria fetuses and quantified the expression of key HPA and HPG components in three brain regions: prefrontal cortex, hypothalamus, and striatum. Results We found an interaction between sex and IUP in the mineralocorticoid receptor (MR), gonadotropin-releasing hormone receptor (GNRHR), androgen receptor (AR), and estrogen receptor alpha (ESR1). IUP was significant in both gonadotropin-releasing hormone (GnRH) and its receptor GNRHR, but in different ways. In the hypothalamus, fetuses adjacent to same-sex neighbors had higher expression of GnRH than fetuses neighboring the opposite sex. Conversely, in the cortex, GNRHR exhibited the inverse pattern, and fetuses that were neighboring the opposite sex had higher expression levels than those neighboring the same sex. Regardless of IUP, in most components that showed significant sex differences, female fetuses had higher mRNA expression levels than male fetuses. We also found that HPA and HPG components were highly related in the early stages of gestation, and that there was an interaction between sex and developmental stage. In the early stages of pregnancy, female component expression levels were more correlated than males’, but in the last trimester of pregnancy, male components were more related to each other than female’s. Conclusions This study suggests that there are sexually different mechanisms to regulate the HPA and HPG axes during fetal development. Higher mRNA expression levels of endocrine axes components may be a mechanism to help females cope with prolonged androgen exposure over a long gestational period. Additionally, these findings suggest different coordination requirements of male and female endocrine axes during stages of fetal development.

Adrenal schwannoma is a rare tumor of Schwann cell origin that represents less than 0.2% of all adrenal tumors. These typically benign tumors are most often found in the head, neck, and limbs. However, schwannomas can also rarely occur rarely in the adrenal gland within the retroperitoneal cavity. In the adrenal gland, these tumors arise from the medulla and are difficult to diagnose, often misdiagnosed as other benign or malignant entities. In this article, we report the case of a 43-year-old female with a large left adrenal mass revealed by biopsy to be a schwannoma. We focus on the use of radiological imaging modalities and immunohistochemical analysis to optimize diagnosis and treatment intervention of this rare tumor.

Nanophotonic structures have shown promising routes to controlling and enhancing nonlinear optical processes at the nanoscale. However, most nonlinear nanostructures require a handling substrate, reducing their application scope. Due to the underwhelming heat dissipation, it has been a challenge to evaluate the nonlinear optical properties of free-standing nanostructures. Here, we overcome this challenge by performing shot-controlled fifth harmonic generation (FHG) measurements on a SiC meta-membrane – a free-standing transmission metasurface with pronounced optical resonances in the mid-infrared (λ res ≈ 4,000 nm). Back focal plane imaging of the FHG diffraction orders and rigorous finite-difference time-domain simulations reveal at least two orders of magnitude enhancement of the FHG from the meta-membrane, compared to the unstructured SiC film of the same thickness. Single-shot measurements of the meta-membrane with varying resonance positions reveal an unusual spectral behavior that we explain with Kerr-driven intensity-dependent resonance dynamics. This work paves the way for novel substrate-less nanophotonic architectures.